The goals of this research are to develop advanced MRS and imaging techniques and to apply them and other complementary methods to studying brain metabolism, neurotransmission and enzyme activity. MRS allows measurement of neurotransmission of glutamate and GABA in vivo, which play important roles in many major psychiatric diseases including depression and schizophrenia. During 2014-2015, we have made significant progress in the development and applications of novel spectroscopic and imaging techniques for studying metabolism and neurotransmission in vivo in the brain. We have succeeded in routinely obtaining high quality MRS data using a 7 Tesla whole body scanner for measuring glutamate, glutamine and glutathione. This method has been recently validated for its high reproducibility (Reliability of 7T 1 H-MRS measured human prefrontal cortex glutamate, glutamine, and glutathione signals using an adapted echo time optimized PRESS sequence: A between- and within-sessions investigation. Lally N, An L, Banerjee D, Niciu MJ, Luckenbaugh DA, Richards EM, Roiser JP, Shen J, Zarate CA Jr, Nugent AC. J Magn Reson Imaging. 2015 Jun 7. doi: 10.1002/jmri.24970.). We have demonstrated that our 7 Tesla single-shot method can be used to measure the kinetics of 13C label incorporation into amino acid neurotransmitters (Detection of glutamate, glutamine, and glutathione by radiofrequency suppression and echo time optimization at 7 tesla. An L, Li S, Murdoch JB, Araneta MF, Johnson C, Shen J.Magn Reson Med. 2015 Feb;73(2):451-8 and L. An, S. Li, J.B. Murdoch, M.F. Araneta, C. Johnson, and J. Shen, In Vivo Detection of 13C Labeling of Glutamate and Glutamine Using Proton MRS at 7T, International Society for Magnetic Resonance in Medicine annual meeting, 2015.). We have also developed a technique that can reliably extract magnetic resonance spectroscopy signals according to irregularly shaped anatomical boundaries (L. An, and J. Shen, Regularized image-guided spatial localization of heterogeneous compartments for magnetic resonance, Med. Phys., in press.).